the best moment would be when most of his weight is about to be put on that leg or during that time. The moment right after a step in, or while he is recovering from a missed kick, or when he is standing on one leg. When timed right, a leg kick will make him fall on the floor, even without using so much force to break his leg.

I like to hit low kicks when my opponent is stepping forward, so as to disrupt their footing, or when my opponent is flat-footed and heavy on the lead leg, allowing me a stationary target so I can load up and do some damage.
Another approach is to force the opponent to retreat, then attack the leg they leave behind, as Mauricio "Shogun" Rua did to Lyoto ...